15-42745313-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_173500.4(TTBK2):c.*482C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0531 in 186,116 control chromosomes in the GnomAD database, including 659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (640 hom., cov: 32)
  • Exomes 𝑓: 0.019 (19 hom.)
• Consequence: TTBK2 NM_173500.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.127

Genes affected

TTBK2 (HGNC:19141): (tau tubulin kinase 2) This gene encodes a serine-threonine kinase that putatively phosphorylates tau and tubulin proteins. Mutations in this gene cause spinocerebellar ataxia type 11 (SCA11); a neurodegenerative disease characterized by progressive ataxia and atrophy of the cerebellum and brainstem. [provided by RefSeq, Aug 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 15-42745313-G-C is Benign according to our data. Variant chr15-42745313-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 315973.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTBK2	NM_173500.4	c.*482C>G		3_prime_UTR_variant	15/15	ENST00000267890.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTBK2	ENST00000267890.11	c.*482C>G		3_prime_UTR_variant	15/15	5	NM_173500.4	P1

Frequencies

GnomAD3 genomes AF: 0.0605 AC: 9201 AN: 152120 Hom.: 638 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0255

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.0589

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.00509

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.0440

GnomAD4 exome AF: 0.0193 AC: 654 AN: 33880 Hom.: 19 Cov.: 0 AF XY: 0.0198 AC XY: 353 AN XY: 17840

Gnomad4 AFR exome AF: 0.192

Gnomad4 AMR exome AF: 0.0131

Gnomad4 ASJ exome AF: 0.0353

Gnomad4 EAS exome AF: 0.0692

Gnomad4 SAS exome AF: 0.0266

Gnomad4 FIN exome AF: 0.00168

Gnomad4 NFE exome AF: 0.00940

Gnomad4 OTH exome AF: 0.0191

GnomAD4 genome AF: 0.0606 AC: 9222 AN: 152236 Hom.: 640 Cov.: 32 AF XY: 0.0587 AC XY: 4371 AN XY: 74432

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.0255

Gnomad4 ASJ AF: 0.0329

Gnomad4 EAS AF: 0.0591

Gnomad4 SAS AF: 0.0290

Gnomad4 FIN AF: 0.00509

Gnomad4 NFE AF: 0.0107

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0373 Hom.: 49

Bravo AF: 0.0666

Asia WGS AF: 0.0490 AC: 173 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spinocerebellar ataxia type 11 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.26
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16957120; hg19: chr15-43037511;